The current application proposes two related studies to examine stressors as risk factors in unipolar depression. The objective of the first study is to determine the relationship of acute and chronic stressors to depressive episode onset (a) in patients with first episode vs recurrent major depression and (b) in cases compared to age, sex, and race-matched community controls. This case-control study will control for personality, attitudinal, and other sociodemographic variables implicated in the onset of depression. We hypothesize that the incidence of fateful (i.e. independent of a person's state, behavior, or action), undesirable, disruptive events and conditions will be significantly greater for (a) first vs multiple episode patients, and (b)for each patient group vs nondepressed community controls. 75 inpatients with DSM-III-R (unipolar) depression and 75 matched Epidemiological Catchment Area controls will be studied. Stressors will be assessed using a comprehensive interview for which empirical data indicate high reliability across (a) interviewers and (b) clinicians rating presence and characteristics of stressors. The objective of the second study is to determine the relationship of stressors to treatment course after 6-weeks of standardized antidepressant treatment and at 6-month follow-up. Sociodemographic and clinical variables associated with outcome will be controlled. The same patient sample will be followed to test four hypotheses: (a) patients with fateful, undesirable, and disruptive life events prior to treatment will have a better response at 6-weeks; (b) those with such events in the 6- months after start of treatment will be more symptomatic at follow-up; (c) patients with chronic stressors at start of treatment will have a better response at 6-weeks; (d) but will have more symptoms at follow-up if chronic stressors are ongoing. Recent theoretical formulations and empirical work suggest that exposure to stressful life events and chronic conditions is a potent psychosocial risk factor for depression. Determination of the contribution of stressors to depression, while controlling for other potential risk factors, is essential to the development of an integrated etiological model of depression. Such data, as well as treatment course data, have practical applications for treatment interventions and prevention strategies. Targeting specific aspects of the psychosocial situation (such as certain stressful experiences or the prevention of certain stressful experiences) can contribute to the precision, and thus the effectiveness, of the intervention. Further, even if drug treatment accounts for much of the variance in successful acute care, stressors may relate to drug treatment failure, and certainly may play a role in longer term care.